--- res: bibo_abstract: - Myopia, or near-sightedness, is an ocular refractive error of unfocused image quality in front of the retinal plane. Individuals with high-grade myopia (dioptric power greater than -6.00) are predisposed to ocular morbidities such as glaucoma, retinal detachment, and myopic maculopathy. Nonsyndromic, high-grade myopia is highly heritable, and to date multiple gene loci have been reported. We performed exome sequencing in 4 individuals from an 11-member family of European descent from the United States. Affected individuals had a mean dioptric spherical equivalent of -22.00 sphere. A premature stop codon mutation c.157C>T (p.Gln53*) cosegregating with disease was discovered within SCO2 that maps to chromosome 22q13.33. Subsequent analyses identified three additional mutations in three highly myopic unrelated individuals (c.341G>A, c.418G>A, and c.776C>T). To determine differential gene expression in a developmental mouse model, we induced myopia by applying a -15.00D lens over one eye. Messenger RNA levels of SCO2 were significantly downregulated in myopic mouse retinae. Immunohistochemistry in mouse eyes confirmed SCO2 protein localization in retina, retinal pigment epithelium, and sclera. SCO2 encodes for a copper homeostasis protein influential in mitochondrial cytochrome c oxidase activity. Copper deficiencies have been linked with photoreceptor loss and myopia with increased scleral wall elasticity. Retinal thinning has been reported with an SC02 variant. Human mutation identification with support from an induced myopic animal provides biological insights of myopic development.@eng bibo_authorlist: - foaf_Person: foaf_givenName: Khanh foaf_name: Tran Viet, Khanh foaf_surname: Tran Viet - foaf_Person: foaf_givenName: Caldwell foaf_name: Powell, Caldwell foaf_surname: Powell - foaf_Person: foaf_givenName: Veluchamy foaf_name: Barathi, Veluchamy foaf_surname: Barathi - foaf_Person: foaf_givenName: Thomas foaf_name: Klemm, Thomas foaf_surname: Klemm - foaf_Person: foaf_givenName: Sebastian foaf_name: Maurer Stroh, Sebastian foaf_surname: Maurer Stroh - foaf_Person: foaf_givenName: Vachiranee foaf_name: Limviphuvadh, Vachiranee foaf_surname: Limviphuvadh - foaf_Person: foaf_givenName: Vincent foaf_name: Soler, Vincent foaf_surname: Soler - foaf_Person: foaf_givenName: Candice foaf_name: Ho, Candice foaf_surname: Ho - foaf_Person: foaf_givenName: Tammy foaf_name: Yanovitch, Tammy foaf_surname: Yanovitch - foaf_Person: foaf_givenName: Georg foaf_name: Schneider, Georg foaf_surname: Schneider foaf_workInfoHomepage: http://www.librecat.org/personId=329095A0-F248-11E8-B48F-1D18A9856A87 - foaf_Person: foaf_givenName: Yi foaf_name: Li, Yi foaf_surname: Li - foaf_Person: foaf_givenName: Erica foaf_name: Nading, Erica foaf_surname: Nading - foaf_Person: foaf_givenName: Ravikanth foaf_name: Metlapally, Ravikanth foaf_surname: Metlapally - foaf_Person: foaf_givenName: Seang foaf_name: Saw, Seang foaf_surname: Saw - foaf_Person: foaf_givenName: Liang foaf_name: Goh, Liang foaf_surname: Goh - foaf_Person: foaf_givenName: Steve foaf_name: Rozen, Steve foaf_surname: Rozen - foaf_Person: foaf_givenName: Terri foaf_name: Young, Terri foaf_surname: Young bibo_doi: 10.1016/j.ajhg.2013.04.005 bibo_issue: '5' bibo_volume: 92 dct_date: 2013^xs_gYear dct_language: eng dct_publisher: Cell Press@ dct_title: Mutations in SCO2 are associated with autosomal-dominant high-grade myopia@ fabio_hasPubmedId: '23643385' ...